In a phase III trial (OVAL Study/GOG 3018) reported in the Journal of Clinical Oncology, Arend et al found that the addition of ofranergene obadenovec to paclitaxel did not improve survival outcomes in patients with platinum-resistant ovarian cancer. Ofranergene obadenovec is a gene-based targeted therapy with a dual mechanism of action consisting of vascular disruption and induction of immune infiltration in solid tumors.
Study Details
In the double-blind trial, 409 patients from sites in the United States, Israel, Spain, Poland, and Japan were randomly assigned between December 2017 and March 2022 to intravenous ofranergene obadenovec (1 × 1013 viral particles every 8 weeks) with paclitaxel at 80 mg/m2 once a week (n = 204) or placebo plus paclitaxel (n = 205), with paclitaxel given until disease progression.
The mean number of previous lines of anticancer therapies was three, with 62% of patients receiving at least three previous lines. The dual primary endpoints were overall survival and progression-free survival on blinded independent central review.
Key Findings
At primary analysis, median progression-free survival was 5.29 months (95% confidence interval [CI] = 4.04–5.49) in the ofranergene obadenovec group vs 5.36 months (95% CI = 4.83–5.55) in the control group (hazard ratio [HR] = 1.03, 95% CI = 0.83–1.29, P = .7823). At interim analysis, median overall survival was 13.37 months (95% CI = 10.84–14.72) in the ofranergene obadenovec group vs 13.14 months (95% CI =11.60–15.84) in the control group (HR = 0.97, 95% CI = 0.75–1.27, P = .8440).
The objective response rate by Response Evaluation Criteria in Solid Tumors, version 1.1, was 28.9% (95% CI = 22.76–35.90) in the ofranergene obadenovec arm, with complete responses in 2.8%, vs 29.6% (95% CI = 23.41–36.67) in the control group, with complete responses in 2.2%.
As noted by the investigators, progression-free survival and objective response in the control group (placebo/paclitaxel) were both numerically better than expected based on findings in the AURELIA trial chemotherapy control group in this setting. In this group, median progression-free survival was 3.4 months and the objective response rate was 11.8%.
CA-125 response was a prognostic factor for progression-free and overall survival in both treatment arms. In the ofranergene obadenovec arm, the hazard ratio for progression-free survival in CA-125 responders compared with that in nonresponders was 0.2428 (95% CI = 0.1642–0.3588). For overall survival, the hazard ratio was 0.3343 (95% CI = 0.2134–0.5238).
The safety profile for ofranergene obadenovec was characterized by common transient flu-like symptoms such as fever and chills.
The investigators concluded: “The addition of [ofranergene obadenovec] to paclitaxel did not improve [progression-free or overall survival]. The [progression-free survival and objective response rate] in the control arm exceeded the results that were anticipated on the basis of the AURELIA chemotherapy control arm. CA-125 response was a substantial prognostic biomarker for [progression-free and overall survival] in patients with [platinum-resistant ovarian cancer] treated with paclitaxel.”
Richard T. Penson, MD, MRCP, of the Division of Medical Gynecologic Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, is the corresponding author for the study.
Disclosure: The study was supported by VBL Therapeutics. For full disclosures of the study authors, visit ascopubs.org.
